Downregulation of platelet-derived growth factor receptor-β in Shp-2 mutant fibroblast cell lines

Abstract

The SH2-containing tyrosine phosphatase Shp-2 appears to function downstream of a variety of growth factor receptors and might play a positive role in cell proliferation. Here we report that expression of the β subunit of platelet-derived growth factor receptor (PDGFR-β) was specifically downregulated in mutant fibroblasts lacking a functional Shp-2, while the levels of PDGFR-α EGFR and IGFIR were not changed. PDGF-stimulated DNA synthesis and extracellular signal regulated kinase (Erk) activation was severely suppressed in mutant cells. RasGAP, that responds to activation of PDGFR-β but not PDGFR-α, was not phosphorylated on tyrosine in mutant cells upon PDGF-treatment. Northern blot analysis failed to detect PDGFR-β mRNA in mutant cells. The transcription initiation from the PDGFR-β gene promoter was not significantly changed, but the half-life of its mRNA was shortened in Shp-2 mutant cells. These observations indicate that Shp-2 not only participates in transmission of signals from growth factor receptors but also plays a specific role in the control of the PDGFR-β expression. We propose that this is an important mechanism for the positive control of cell proliferation by Shp-2.